ESPE Abstracts

Background: STAT5B deficiency is characterized by severe postnatal growth failure, low IGF1, elevated levels of GH and prolactin, and immunodeficiency. To date, only ten patients with seven different mutations have been described.

Objective and hypotheses: Describe clinical characteristics of a novel homozygous frameshift mutation in STAT5B.

Results: A 17-year-old female was referred for proportionate short stature and primary amenorrhea. She was born at term with a normal birth weight; her short stature became evident after 2 years. She had no history of severe or recurrent infections, or pulmonary disease. Parents were first cousins and target height was 152.2 cm (−1.3 SDS). At first evaluation (15.2 years) height SDS was −6.2, weight SDS −4.1, delayed pubertal development (Tanner stage B2P2), and bone age was retarded by 4 years. She had midface hypoplasia, frontal bossing, high-pitched voice, and normal intelligence. Examination of the skin revealed generalized ichthyosis and, erythema and papules on hands. A biopsy of the lesions led to a diagnosis of chronic dermatitis. Serum IGF1 was undetectable and IGFBP3 was 0.5 mg/l, with persistently elevated prolactin (97–139 ng/ml). Results of two GH provocation tests showed GH peaks of 0.7 and 3.8 ng/ml. Cranial and pituitary MRI were normal. hGH treatment, however, did not significantly improve serum IGF1 levels or increase growth rate. Targeted gene analysis identified a novel homozygous frameshift mutation in the STAT5B gene, exon 12: c.1453del, p.Asp485Thrfs*29, which segregated appropriately. Absolute lymphocyte counts were in normal ranges. However, she had low CD3⁺ T cell, elevated CD19⁺B cell and normal NK cell counts. FOXP3⁺ expression on CD4⁺CD25⁺ cells was normal. In vitro T lymphocyte proliferative blastogenesis in response to stimulation with CD3 were also normal.

Conclusion: Severe immunodeficiency and chronic pulmonary fibrosis, present in all but two previously reported patients, are not obligatory features in patients with STAT5B deficiency.